ACM  >> Vol. 4 No. 3 (September 2014)

    The Progress in the Study of the Correlation between the WNK1 Gene and Primary Hypertension

  • 全文下载: PDF(337KB) HTML    PP.47-52   DOI: 10.12677/ACM.2014.43009  
  • 下载量: 1,270  浏览量: 4,906  


王 莉:内蒙古医科大学附属医院,呼和浩特;

原发性高血压WNK1基因Gordon综合征离子转运Essential Hypertension Wnk1 Gene Gordon Syndrome Iron Transport



WNK1 was the first member found in WNK family; it has multiple transcription start sites and dif-ferent transcription products in different tissues. Further researches found that the deletion of Intein-1 in WNK1 gene can lead to Gordon syndrome. WNK1 is a regulatory protein of the renal iron transporters and channels, and plays a very important role in maintaining renal potassium, sodium and chlorine ions balance as well as the regulation of blood pressure, so the WNK1 gene is considered a key genes for essential hypertension. In addition, the WNK1 gene polymorphism may be linked to the susceptibility of the essential hypertension in general population. This review shows the source, structure and function of the WNK1, and investigates the correlation between primary hypertension and WNK1 aimed at guiding anti-hypertensive drugs clinical drug regiments and forecasts.

王莉, 于赛华. WNK1与原发性高血压相关性研究进展[J]. 临床医学进展, 2014, 4(3): 47-52.


[1] Cope, G., Golbang, A. and O’Shaughnessy, K.M. (2005) WNK kinases and the control of blood pressure. Pharmacol-ogy Therapeutics, 106, 221-231.
[2] Subramanya, A.R., Yang, C.L., Zhu, X., et al. (2006) Dominant-negative regu-lation of WNK1 by its kidney-specific kinase-defective isoform. American Journal of Physiology. Renal Physiology, 290, F619-F624.
[3] Delaloy, C., Lu, J., Houot, A.M., et al. (2003) Multiple promoters in the WNK1 gene: One controls expression of a kidney-specific kinase-defective isoform. Molecular and Cellular Biology, 23, 9208-9221.
[4] O’Reilly, M., Marshall, E., Speirs, H.J., et al. (2003) WNK1, a gene within a novel blood pressure control pathway, tissue-specifically generates radically different isoforms with and without a kinase domain. Journal of the American Society of Nephrology, 14, 2447-2456.
[5] Hadchouel, J., Delaloy, C., Faure, S., et al. (2006) Familial hyperkalemic hypertension. Journal of the American Society of Nephrology, 17, 208-217.
[6] Golbang, A.P., Murthy, M., Hamad, A., et al. (2005) A new kindred with pseudohypoaldosteronism type II and a novel mutation (564D>H) in the acidic motif of the WNK4 gene. Hypertension, 46, 295-300.
[7] Yang, C.L., Zhu, X. and Ellison, D.H. (2007) The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex. The Journal of Clinical Investigation, 117, 3403-3411.
[8] San-Cristobal, P., de Los, H.P., Ponce-Coria, J., et al. (2008) WNK kinases, renal ion transport and hypertension. American Journal of Nephrology, 28, 860-870.
[9] Liu, F., Zheng, S., Mu, J., Chu, C., Wang, L., Wang, Y., et al. (2013) Common variation in with no-lysine kinase 1 (WNK1) and blood pressure responses to dietary sodium or potassium interventions: Family-based association study. Circulation Journal, 77, 169-174.
[10] Yiannakouris, N., Yannakoulia, M., Melistas, L., Chan, J.L., Klimis-Zacas, D. and Mantzoros, C.S. (2001) The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of bo- dy weight and body composition variability. The Journal of Clinical Endocrinology & Metabolism, 86, 4434-4439.
[11] Xu, B.E., Stippec, S., Chu, P.Y., Lazrak, A., Li, X.J., Lee, B., et al. (2005) WNK1 activates SGK1 to regulate the epithelial sodium channel. Proceedings of the National Academy of Sciences of the United States of America, 102, 10315- 10320.
[12] Naray-Fejes-Tóth, A., Snyder, P.M. and Fejes-Tóth, G. (2004) The kidney-specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport. Proceedings of the National Academy of Sciences of the United States of America, 101, 17434-17439.
[13] Fang, L., Liu, J., Li, D., Yang, C.L., Subramanya, A.R., Maouyo, D., et al. (2006) WNK1 kinase isoform switch regulates renal potassium excretion. Proceedings of the National Academy of Sciences of the United States of America, 103, 8558-8563.
[14] Newhouse, S.J., Wallace, C., Dobson, R., Mein, C., Pembroke, J., Farrall, M., et al. (2005) Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British genetics of hypertension study. Human Molecular Genetics, 14, 1805-1814.
[15] Kahle, K.T., Ring, A.M. and Lifton, R.P. (2008) Molecular physiology of the WNK kinases. Annual Review of Physiology, 70, 329-355.
[16] 刘洁琳, 李梅, 刘雅, 王佐广, 文杰, 张蓓, 等 (2013) WNK1基因单核苷酸多态性位点与高血压患者左心室质量指数的相关性研究.心肺血管病杂志, 4, 1007-5062.
[17] Kimura, T.E., Jin, J., Zi, M., Prehar, S., Liu, W., Oceandy, D., et al. (2010) Targeted deletion of the extracellular signal-regulated protein kinase 5 attenuates hypertrophic response and promotes pressure overload-induced apoptosis in the heart. Circulation Research, 106, 961-970.
[18] Gamba, G. (2005) Role of WNK kinases in regulating tubular salt and potassium transport and in the development of hypertension. American Journal of Physiology, Renal Physiology, 288, F245-F252.
[19] Han Y., Fan, X.H., Sun, K., Wang, X., Wang, Y., Chen, J., et al. (2011) Hypertension associated with hydrochlorothiazide response. Clinical Biochemistry, 44, 1045-1049.